Objectives To determine the inhibition effect of epigallocatechin gallate (EGCG) and green tea extract on neuronal necroptosis based on necroptosis morphology. Methods In vivo study was performed on male Rattus norvegicus middle cerebral artery occlusion (MCAO) model divided into five groups, MCAO-control groups, EGCG 10 mg/kg BW/day, EGCG 20 mg/kg BW/day, EGCG 30 mg/kg BW/day, and green tea extract 30 mg/kg BW/day for 7 days treatment. MCAO model was made by modification method using Bulldog clamp. After 7 days of treatment, all R. norvegicus were sacrificed. After that, examination using Hematoxylin–Eosin stain was conducted to look at necroptosis morphology in each group. Results We found that there are significant differences between control group and the other three groups (EGCG 20 mg/kg BW/day, EGCG 30 mg/kg BW/day, and green tea extract (p<0.05). There is a significant correlation between the number of neuron cell necroptosis and both EGCG and green tea extract (p<0.05). The correlation is negative, which means both EGCG and green tea extract will decrease the number of neuron cell necroptosis. EGCG will decrease neuron cell necroptosis starting from the dose of 20 mg/kg BW/day. EGCG 30 mg/kg BW/day produces the best result compared to other doses. Conclusions Camellia sinensis (green tea) with its active compound EGCG decreases neuronal necroptosis morphology in MCAO models.

Objectives To determine the effect of green tea with the active ingredient epigallocathechin-3-gallate (EGCG) on the inhibition of apoptosis in the middle cerebral artery occlusion (MCAO) model. Methods Four month old male Rattus norvegicus rats with a body weight of 200–275 g was used for the MCAO model and divided into five groups, and the treatment was carried out for 7 days. Before being sacrificed, the subject had 1 cc of blood drawn for high mobility group box 1 (HMGB-1) examination using enzyme-linked immunosorbent assay (ELISA), and after being sacrificed, the brain tissue specimen was taken to examine caspase-3 and B-cell lymphoma 3 (BCL-3) using immunohistochemistry methods. Results There was no significant difference in HMGB-1 results for the treatment group compared to the control group (P1: 384.20 ± 231.72 [p = 0.553]; P2: 379.11 ± 268.4 [p = 0.526]; P3: 284, 87 ± 276.19 [p = 0.140]; P4: 435.32 ± 279.95 [p = 0.912]). There is a significant increase in BCL-2 expression between the treatment group compared to the control group (P1: 2.58 ± 0.51 [p = 0.04]; P2: 3.36 ± 0.50 [p<0.001]; P3: 4.00 ± 0.42 [p<0.001]; P4: 3.60 ± 0.52 [p<0.001]). There was a significant difference in caspase-3 expression compared to the control group in the P3 group (P1: 4.33 ± 0.49 [p = 0.652]; P2: 4.09 ± 0.30 [p = 0.136]; P3: 3.58 ± 0.51 [p = 0.01]; P4: 3.89 ± 0.42 [p = 0.063]). There is no correlation between HMGB-1 and caspase-3 (r = −0.063; p = 0.613) or BCL-2 (r = −0.106; p = 0.396). There is significant negative correlation between caspase-3 and BCL-2 (r = −0.459; p = 0.000). Conclusions Green tea with the active ingredient EGCG can inhibit neuronal cell death through the apoptotic pathway and not through the activation of HMGB-1.

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Background & Objectives: Treatment of chronic pain using NSAIDs, steroids, opioids, and herbs has been associated with many complications with the long-term use. Wet cupping therapy (WCT) has been used to reduce pain, by triggering mu opioid receptor expression. We conducted this study to compare the effectiveness between WCT with oral opioids for pain management. Methodology: It was an experimental study with randomized control group post-test only design. Thirty two male white rats of strain Wistar were divided into four groups: (1) Group-NC; mice in this group were given nothing as a negative control group, (2) Group-CFA; group that was given Complete Freund’s Adjuvant (CFA) only as a positive control group, (3) Group-WCT; mice were given CFA and WCT, and (4) Group-O was given CFA and oral opioids. The measured variables were pain threshold value and mu opioid receptors. Statistical analysis was done us(ing SPSS software (version 22.0, Chicago, IL). Results: The results showed no significant differences in the expression of mu opioid receptors between Group-NC and Group-CFA (p = 0.061). There were significant differences in the expression of opioid receptors between Group-CFA and Group-WCT (p < 0.001), and also between WCT group and Group-O (p = 0.002). The differences of pain threshold value were only significant between Group-NC (p = 0,006) and Group-CFA (p = 0,013) with Group-O. Conclusion: Wet cupping therapy triggers the expression of mu opioid receptors. Wet cupping therapy as effective in relieving pain as opioids. Citation: Subadi I, Kusumawardani MK, Qorib MF, Susilo I, Hidayati HB. Wet cupping therapy improves mu opioid receptor expression and pain threshold in animal models of inflammation. Anaesth pain & intensive care 2019;23(4):__   Received: 6 February 2019; Reviewed: 16 February 2019, 2 August 2019; Revised: 9 September 2019; Accepted: 15 September 2019

Objectives This study was designed to evaluate the potential of Andrographis paniculata ethanolic extract to inhibit the increase in proliferation and induction of abnormal cell death. Methods The hyperplasia stage as an early stage of cancer development was induced by oral administration of 20 mg/Kg BW DMBA to SD rats twice a week for 5 weeks. There were five groups in this study include negative control, positive control, and treatment groups of DMBA induction followed by administration of A. paniculata ethanolic extract in doses equivalent to 10, 30 or 100 mg/Kg BW andrographolide once per day for 6 consecutive weeks. On the last day, rats were sacrificed, lung and colon tissues were collected. Histological examination by HE staining and immunohistochemistry using p53, telomerase, and caspase-3 antibodies were aimed at observing hyperplasia state in these tissues. Results DMBA induction to SD rats was able to produce hyperplasia in lung parenchymal and colon epithelial tissue. This can be showed by the increasing number of proliferated cells and as indicated by the number of brown-colored nuclei with sharper intensity. As well telomerase appears to be overexpressed strongly, while p53 and caspase-3 show low intensity. The administration of A. paniculata extract for 6 weeks showed a decrease in the number of cells that actively proliferate, a decrease in telomerase activity, and an increase in caspase-3 levels which indicate cellular death activity. Conclusions A. paniculata ethanolic extract can inhibit the development of cancer at the hyperplasia stage by reducing telomerase activity and increasing apoptosis, marked by an increase of caspase-3 expressions.